It is often desired to immediately introduce an active agent into a fluid system yet delay its reaction with components of the system until after some other desired result is achieved. The disinfecting of soft contact lenses with hydrogen peroxide and subsequent neutralization of residual H.sub.2 O.sub.2 presents such a situation.
The use of hydrogen peroxide systems for disinfecting soft contact lenses is well known for its efficacy. Such a use requires that residual hydrogen peroxide remaining on the lenses after disinfecting must be neutralized or decomposed to a biologically inert state before the disinfected lenses may be placed on the eyes. Significant residual H.sub.2 O.sub.2 remaining on the lenses results in eye irritation, generally manifested by stinging sensations.
A number of neutralizing or reducing agents are known in the art. For example, U.S. Pat. No. 3,912,451 teaches neutralizing residual hydrogen peroxide by contacting the disinfecting solution with lenses therein with a metal catalyst, such as platinum, that catalyzes decomposition. A difficulty with these catalytic metal systems is that an excessive, inconvenient amount of time is required to reduce the solution hydrogen peroxide residues to a safe level.
Other agents are known in the art for decomposing hydrogen peroxide at a faster, more convenient rate. Of particular interest is the use of an enzyme, such as catalase. For example, U.S. Pat. Nos. 4,748,992 and 4,585,488 teach sterilizing contact lenses with H.sub.2 O.sub.2 and subsequently contacting the lenses with an isotonic solution of dissolved catalase, resulting in effective decomposition of residual H.sub.2 O.sub.2 taking place within a few minutes.
In addition to the relative effectiveness of disinfecting/neutralizing chemicals per se, a major goal in designing lens care methods and formulations relates to simplifying their methods of use. It is widely accepted that regimens for disinfecting and cleaning contact lenses must be as simple as possible to encourage lens wearers to comply with the care regimens as a matter of avoiding adverse health effects due to contaminated lenses. Any simplification in a regimen, such as by combining processing steps, combining chemicals, or adding separate components at the same time, is generally advantageous in achieving patient compliance.
Simplifying lens care regimens by combining disinfecting and neutralizing components remains difficult to achieve because of the difficulty of balancing the relative reaction rates of the disinfecting and neutralizing processes. A difficulty with fast neutralizing of H.sub.2 O.sub.2 systems, such as catalase, is that the lenses, to be effectively disinfected, must be exposed to a relatively high concentration of H.sub.2 O.sub.2 for a significant, finite period of time in order to achieve disinfecting before neutralizing proceeds significantly. The time required for disinfection is generally dependent upon the concentration of hydrogen peroxide utilized, requiring on the order of two hours at 1.0 weight percent H.sub.2 O.sub.2 while only five minutes at 3.0% by weight hydrogen peroxide.
Since it is preferred that H.sub.2 O.sub.2 concentration be as low as possible, it is evident that if one desires to treat lenses simultaneously with hydrogen peroxide disinfectant and a fast acting neutralizion such as catalase, it is necessary to employ the neutralizer with care. In fact, it is preferable to delay the effective release of such a neutralizer, in order to allow for adequate time to achieve disinfecting and, thereafter, obtain substantially complete neutralization of the disinfecting hydrogen peroxide component.
A number of proposals have been made for delaying release of the neutralizing agent until after the disinfecting step is at least substantially complete. For example, Kruse, et al., in U.S. Pat. No. 4,767,559, form a one step cleaning/disinfecting tablet that includes an outer layer that is the disinfecting component and a core that comprises the neutralizing agent. The disinfecting agent may be any acid-reacting, H.sub.2 O.sub.2 -generating compound such as potassium persulfate, melamine perhydrate or, preferably, urea peroxhydrate. The core neutralizing agent comprises a reducing agent, such as ascorbic acid or glucose or an enzyme, such as catalase. In operation, the disinfecting agent first dissolves, then the core dissolves to neutralize the cleaning agent. A difficulty with this product is that the process for making such an outer layered/core tablet is complex which adds significant cost such that no commercial product has yet been successfully marketed using this concept.
Kaspar et al, in U.S. Pat. No. 4,568,517, describe simultaneously contacting lenses with a hydrogen peroxide solution and a neutralizing agent, preferably sodium thiosulfate or sodium sulfite, in a solid form such as a tablet. The neutralizer agent is provided with a coating which dissolves gradually to release neutralizer only after the disinfecting period has elapsed. The H.sub.2 O.sub.2 solution transformed in situ into a buffered saline lens storage solution having a pH of 6.5-8.5 and a tonicity of 200-450 milliosmol per kg solution. A difficulty with the preferred sodium thiosulfate tablet is that it is very large in size, making this approach impractical.
A further difficulty with controlled release systems is that of providing adequate flexibility in release times and profiles, as well as good uniformity of release. Schafer et al., in U.S. Pat. No. 5,011,661, describes controlled release of neutralizing agent into a peroxide system through an insoluble, yet semi-permeable membrane coating or capsule. The membrane comprises various polymers and triacetin for controlling release. Park et al., in U.S. Pat. No. 5,145,644, describes a method of coating a tablet with a controlled release water soluble polymer employing a water and ketone solvent. The ketone containing solvent is said to produce increased uniformity of coating.
It is quite evident that improvements in controlled release products and methods are desirable that provide for increased flexibility and uniformity of delivery of an active agent into a aqueous system. The need is particularly evident for a delayed release composition and method that delivers a neutralizer such as catalase into a hydrogen peroxide disinfecting system such that the neutralizer is precisely timed and uniformly delivered wherein the disinfecting step is achieved without premature neutralization.